Langerhans cells are immunologically important cells which have been shown to be involved in antigen presentation, immunosurveillance of viral and tumor antigens and allogeneic graft rejection. Their non-uniform distribution in oral mucosae and decreased numbers in tissues of aged individuals makes information concerning their rate of local proliferation, rate of migration from bone marrow precursors, and their homing mechanisms, of great importance. This information is essential if manipulation of Langerhans cells is to be attempted to maintain optimal numbers in these tissues. The proposed studies use a well characterized animal implant system between histocompatible mice, and radiation chimeras between C3H parental mice and F1 hybrids, to investigate environmental influences on the rate of replacement of Langerhans cells. At varying periods of time from preparation of implants or chimeras, mice will be injected with 5-bromodeoxyuridine (BrdU), sacrificed and epithelial cell suspensions prepared. Using fluorescent labelled monoclonal antibodies and FACS sorting, Langerhans cells of C3H and F1 phenotypes will be separated smears prepared and BrdU labelled cells identified to determine local proliferation. Local proliferation will be determined by demonstration of BrdU on smears. Total numbers of Langerhans cells of each phenotype and of BrdU labelled cells for each time period will be determined. To determine if source of replacement is by central bone marrow control or by demand from individual sites, some radiation chimeras will have one ear treated to induce hyperplasia and will then be tested as above. The presence of homing mechanisms in the local vasculature or in the epithelial microenvironment will be investigated by injecting mice containing implants with a suspension of Langerhans cells.